Abstract 267P
Background
The MORPHEUS platform consists of multiple, global, open-label, randomized phase Ib/II trials designed to identify early efficacy signals and safety of treatment (tx) combinations across cancers. Within MORPHEUS, atezo (anti–PD-L1) was tested with entino, an HDAC inhibitor, in patients (pts) with locally advanced or metastatic (m) HR+ HER2- breast cancer (NCT03280563). Entino can inhibit immune suppressor cells and thus has potential to improve atezo efficacy.
Methods
Eligible pts with 2L/3L HR+ chemotherapy-naive BC with prior CDK4/6 inhibitor treatment were randomized to either atezo (1200 mg IV q3w) with entino (5 mg oral days 1, 8, 15) or fulvestrant (control). The primary endpoint was overall response rate (ORR). Progression-free survival (PFS) and overall survival (OS) were secondary endpoints.
Results
15 pts were randomized to atezo + entino and 14 to fulvestrant. Pts were followed for ≥ 18 wk (data cutoff: 18 June 2020). Confirmed ORRs were 6.7% (95% CI: 0.17, 31.95) and 0% (95% CI: 0, 23.16), respectively. Duration of response was 2.5 months for atezo+entino (N/A for control). Median PFS was 1.8 months (95% CI: 1.5, 3.6) and 1.8 months (95% CI: 1.5, 2.7), respectively. Updated survival data will be presented. Respectively, 40.0% and 21.4% of pts had Gr 3/4 AEs; no Gr 5 AEs occurred; serious AEs (SAEs) occurred in 26.7% and 14.3% of pts; 6.7% and 0% of pts had tx-related AEs leading to tx withdrawal. The most common tx-related AEs were nausea (33.3%), vomiting (26.7%), fatigue (26.7%), pyrexia (26.7%) and chills (20.0%) with atezo+entino. PD-L1 expression (SP263) was low or absent in most patients, with 33% having PD-L1 ≥1%; expression did not correlate with stable disease or response to therapy for atezo+entino-treated patients. PK data revealed that peak exposure of entino was in line with expectations to inhibit HDAC, and atezo trough concentrations exceeded the target required for maximal receptor occupancy.
Conclusions
Limited efficacy was seen with atezo+entino in this patient population. The safety profile was consistent with each agent’s known safety profile, with no new safety signals identified.
Clinical trial identification
NCT03280563.
Editorial acknowledgement
Legal entity responsible for the study
F. Hoffmann-La Roche, Ltd.
Funding
F. Hoffmann-La Roche, Ltd.
Disclosure
A. Sonnenblick: Financial Interests, Personal, Advisory Role: Novartis, Pfizer, Roche, Renium, Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca. S. Im: Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Pfizer, Eisai, Daewoong Pharma; Financial Interests, Personal, Advisory Role: AstraZeneca, Eisai, GSK, Eli Lilly, MSD, Novartis, Hanmi, Roche. K.S. Lee: Financial Interests, Personal, Advisory Role: Roche, Pfizer, Eli Lilly, Novartis; Financial Interests, Institutional, Research Grant: Dong-A ST. A. Tan: Financial Interests, Personal, Advisory Role: Genentech/Roche,; Financial Interests, Institutional, Research Grant: Genentech/Roche, Merck; Financial Interests, Personal, Invited Speaker: Merck. M. Telli: Financial Interests, Personal, Advisory Role: Merck, Pfizer, Natero, Immunomedics; Financial Interests, Institutional, Research Grant: Genentech/Roche, Bayer, OncoSec, AbbVie, AstraZeneca, Pfizer, Merck, Calithera, EMD Serono, PharmaMar, Tesaro, Vertex. S. Strulov Shachar: Financial Interests, Personal, Speaker’s Bureau: Roche, Medison; Financial Interests, Personal, Advisory Role: Novartis, Pfizer, Eli Lilly. F. Bene Tchaleu: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche. E. Cha: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche. K. DuPree: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche. M. Nikanjam: Financial Interests, Personal, Full or part-time Employment: Genentech/Roche; Financial Interests, Personal, Stocks/Shares: Genentech/Roche. C. Shemesh: Financial Interests, Personal, Stocks/Shares: Roche. J. Xu: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche. X. Zhang: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche. H.S. Rugo: Financial Interests, Institutional, Research Grant: Pfizer, Merck, Novartis, Lilly, Genentech, Odonate, Daiichi, Seattle Genetics, Eisai, Macrogenics, Sermonix, Boehringer Ingelheim, Polyphor, AstraZeneca, Immunomedics; Financial Interests, Personal, Other, Travel Support: Daiichi, Mylan, Pfizer, Merck, AstraZeneca, Novartis, Puma; Financial Interests, Personal, Other, Honoraria: Puma, Mylan, Samsung. All other authors have declared no conflicts of interest.